RESUMEN
BACKGROUND: Ataxia with oculomotor apraxia (AOA) is characterized by early-onset cerebellar ataxia associated with oculomotor apraxia. AOA1, AOA2, AOA3, and AOA4 subtypes may present pathogenic variants in APTX, SETX, PIK3R5, and PNKP genes, respectively. Mutations in XRCC1 have been found to cause autosomal recessive spinocerebellar ataxia-26 (SCAR26) now considered AOA5. OBJECTIVES: To examine a cohort of Brazilians with autosomal recessive cerebellar ataxia plus oculomotor apraxia and determine the frequencies of AOA subtypes through genetic investigation. METHODS: We evaluated clinical, biomarkers, electrophysiological, and radiological findings of 52 patients with AOA phenotype and performed a genetic panel including APTX, SETX, PIK3R5, PNKP, and XRCC1. RESULTS: We found pathogenic variants in SETX (15 patients), PNKP (12), and APTX (5). No mutations in PIK3R5 or XRCC1 were identified. CONCLUSIONS: AOA2 and AOA4 were the most common forms of AOA in Brazil. Mutations in PIK3R5 and XRCC1 were not part of this genetic spectrum. © 2022 International Parkinson and Movement Disorder Society.
Asunto(s)
Apraxias , Ataxia Cerebelosa , Apraxias/congénito , Apraxias/genética , Ataxia/genética , Brasil , Ataxia Cerebelosa/complicaciones , Ataxia Cerebelosa/genética , Síndrome de Cogan , ADN Helicasas/genética , Enzimas Reparadoras del ADN/genética , Humanos , Enzimas Multifuncionales/genética , Mutación/genética , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , ARN Helicasas/genética , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos X/genéticaRESUMEN
BACKGROUND: Ataxia telangiectasia is one of the most common causes of autosomal recessive cerebellar ataxias. However, absence of telangiectasia, normal levels of alpha-fetoprotein and negative genetic test may direct to alternative diagnosis with similar phenotypes such as ataxia telangiectasia-like disorders (ATLD). CASES: We report two instructive cases of ATLD: the first case with ataxia telangiectasia-like disorder type 1 related to MRE11A gene, and the second case with ataxia telangiectasia-like disorder type 2 related to PCNA gene. LITERATURE REVIEW: ATLD is an unusual group of autosomal recessive diseases that share some clinical features and pathophysiological mechanisms with ataxia telangiectasia (AT). ATLD may be associated with mutations in the MRE11A (ATLD type 1) and PCNA (ATLD type 2) genes. ATLD belongs to the group of chromosomal instability syndromes. The reason for the term ATLD is related to the similar pathophysiological mechanisms observed in AT, which is characterized by chromosomal instability and radiosensitivity. CONCLUSIONS: In this review, the main clinical features, biomarkers, brain imaging and genetics of ATLD are discussed. Mutations in the MRE11A and PCNA genes should be included in the differential diagnosis for early onset cerebellar ataxia with absence of telangiectasia and normal levels of alpha-fetoprotein.
